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Mol. Cell. Biol., Jul 1996, 3789-3798, Vol 16, No. 7
X Huet, J Rech, A Plet, A Vie and JM Blanchard
Transcription of the gene coding for cyclin A, a protein required for S-
phase transit, is cell cycle regulated and is restricted to proliferating
cells. To further explore transcriptional regulation linked to cell
division cycle control, a genomic clone containing 5' flanking sequences of
the murine cyclin A gene was isolated. When it was fused to a luciferase
reporter gene, it was shown to function as a proliferation-regulated
promoter in NIH 3T3 cells. Transcription of the mouse cyclin A gene is
negatively regulated by arrest of cell proliferation. A mutation of a
GC-rich sequence conserved between mice and humans is sufficient to relieve
transcriptional repression, resulting in a promoter with constitutively
high activity. In agreement with this result, in vivo footprinting reveals
a protection of the cell cycle-responsive element in G0/early G1 cells
which is not observed at later stages of the cell cycle. Moreover, the
footprint is present in dimethyl sulfoxide-induced differentiating and not
in proliferating Friend erythroleukemia cells. Conversely, two other sites,
which in vitro bind ATF-1 and NF-Y, respectively, are constitutively
occupied throughout cell cycle progression.
Copyright © 1996, American Society for Microbiology
Cyclin A expression is under negative transcriptional control during the cell cycle
Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, France.
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